Rate and equilibrium effects of tert-alkyl groups on rotamerization in 3,4-alkylenedioxy-, 3-alkoxy- and 3,4-dialkoxy-2-thienyl(di-tert-alkyl)methanols: an IR, NMR, kinetics and MM studyElectronic supplementary information (ESI) available: additional experimental data. See http://www.rsc.org/suppdata/p2/b2/b203714a/

Abstract

Di-1-adamantyl and (1-adamantyl)(tert-butyl) analogues are compared with the previously studied 3- or 3- and 4-substituted 2-thienyl(di-tert-butyl)methanols. The equilibrium constants for syn–anti rotamerization ([syn]/[anti]) are slightly greater than for the smaller di-tert-butyl derivatives. In the intramolecularly hydrogen-bonded anti rotamers, neither the 1H NMR shift of the hydroxy proton nor the OH stretching frequency, both indicators of intramolecular hydrogen bond strength, is greatly affected by a change in the tert-alkyl group; these changes in the equilibrium constants must, therefore, be attributed to variations in steric effects. The rotation barriers for the compounds with the larger tert-alkyl groups are much enhanced and better differentiated. In all three sets the syn→anti and anti→syn rotation barriers are linearly correlated, and either can be correlated with the free energy difference. Nevertheless, the data do not meet the criteria for a classical Leffler–Grunwald-type rate-equilibrium relationship. Molecular mechanics calculations (MMFF94 force field) account fairly well for the variation in the free energy difference for rotamer pairs of the di-1-adamantyl, (1-adamantyl)(tert-butyl) and di-tert-butyl derivatives, but slightly overestimate the small differences in the equilibrium constants for the three series. The calculated rotation barriers for the di-tert-butyl compounds are about 7 kcal mol−1 higher than those observed. Those for 2-anisyl-, phenyl- and 2-tolyldialkylmethanols are increasingly overestimated as the rotation barrier rises, but a good correlation ranging over 20 kcal mol−1 is obtained; this correlation is not coincident with that for the thiophene derivatives.